Recommendations for including multiple symptoms as endpoints in cancer clinical trials: a report from the ASCPRO (Assessing the Symptoms of Cancer Using Patient-Reported Outcomes) Multisymptom Task Force.

The multiple symptoms arising from cancer and its treatment impose significant distress for patients. However, in clinical research, there is no agreed-upon way of assessing and presenting the effects of treatment on multiple symptoms, as either individual scores or a composite score. The ASCPRO (Assessing the Symptoms of Cancer Using Patient-Reported Outcomes) Multisymptom Task Force was established to make recommendations about measuring multiple symptoms as outcomes in cancer clinical trials. The Multisymptom Task Force addressed how to choose the symptoms to be assessed and how multiple individual symptom scores or composite scores of several symptoms might be used as clinical trial outcomes. Consensus was reached on a definition of a multisymptom outcome, the problem of source attribution, and the need for a hypothesis-driven conceptual framework to measure multisymptom outcomes. Validated single-item and multi-item measures currently available or that can be easily generated for oncology use were deemed sufficient for measuring multiple symptoms. The relative value of a composite score versus a set of individual symptom scores was discussed, along with issues in developing and deploying such a composite measure. The results indicated that more research on combining scores of different symptoms is needed. Symptom data should be a required component of cancer clinical trials. Patient-reported symptoms provide a unique patient perspective on treatment benefit and risk that goes beyond clinician-reported adverse events. A representation of changes in multiple symptoms would clarify the impact of treatment and enhance the interpretation of cancer clinical trials for clinicians, patients, and those who make health care policy.

Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation.

The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph(+) ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-alpha in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph(+) ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection.

Nonsteroidal anti-inflammatory drugs and risk of prostate cancer in the Baltimore Longitudinal Study of Aging.

BACKGROUND: Laboratory and epidemiologic studies suggest that aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk of cancer, possibly via inhibition of the cyclooxygenase enzymes. We evaluated the association of aspirin and nonaspirin NSAIDs with subsequent prostate cancer in a prospective study. We also assessed whether use of these drugs influences serum prostate-specific antigen (PSA) concentration. METHODS: Participants were 1,244 male members of the Baltimore Longitudinal Study of Aging. Use of prescription and over-the-counter drugs was collected by questionnaire and interview at multiple study visits. One hundred forty-one prostate cancer cases diagnosed between 1980 and May 2004 were confirmed by medical record review. We used Cox proportional hazards regression to estimate the rate ratio (RR) of prostate cancer updating drug use over time and taking into account age and year. We used generalized estimating equations to calculate age-adjusted geometric mean PSA concentration by aspirin or nonaspirin NSAIDs use among 933 of the men without prostate cancer, for whom 3,749 PSA measurements in archived sera had been done previously. RESULTS: On 46.0% and 21.5% of the visits, current use of aspirin or nonaspirin NSAIDs (mostly ibuprofen) was reported, respectively. The RRs of prostate cancer comparing ever to never use were 0.76 [95% confidence interval (95% CI), 0.54-1.07] for aspirin, 0.79 (95% CI, 0.54-1.16) for nonaspirin NSAIDs, and 0.71 (95% CI, 0.49-1.02) for either medication. The association for ever use of either aspirin or nonaspirin NSAIDs was suggestively more pronounced in men <70 years (RR, 0.54; 95% CI, 0.27-1.03) than in men >/=70 years (RR, 0.78; 95% CI, 0.50-1.22; P(interaction) = 0.73). The RR for current use of either drug was attenuated relative to ever use. Mean PSA concentration did not differ between users and nonusers of either aspirin or nonaspirin NSAIDs (1.01 versus 0.98 ng/mL, P = 0.56). CONCLUSION: In this prospective study, men, in particular younger men, who had ever used aspirin or nonaspirin NSAIDs had a modest nonstatistically significant lower risk of prostate cancer. The modest inverse association was unlikely due to detection bias that might have resulted if anti-inflammatory drugs had influenced serum PSA concentration.

Estimation of energy expenditure in Western Samoa, American Samoa, and Honolulu by recall interviews and direct observation.

Reliable and accurate estimates of energy expenditure are a fundamental requirement for research on energy balance, energy flow, and other biocultural phenomena. Cross-validation of estimates derived from more than one time-allocation method can detect sources of bias and may lead to estimates which are more credible than those from activity recalls used alone. This paper compares 24-hour activity recalls and direct observations as methods of estimating the energy expenditure of 145 18-37-year-old Samoans residing in rural Western Samoa, American Samoa, and Honolulu. Daily energy expenditure was estimated on 2 workdays by activity recalls (n = 214) or by focal-individual observations (n = 91). Samoan men expend 2,900-3,400 kcal/day and women expend 2,250-2,650 kcal/day. Estimates of energy expenditure in the Western Samoa sample are comparable to other subsistence horticultural societies, while the American Samoan and Honolulu samples are comparable to other sedentary working populations. Group estimates from recall interviews are 100-400 kcal/day higher than from observations, although this is only a difference of 5-10%. Overestimation of energy expenditure is more evident at higher work intensities than for sedentary activities. The apparent exaggeration of strenuous activity in this, and other, studies indicates that without cross-validation, self-reported activity data may often be confounded by an unknown amount of subjective bias.

Selective migration as a bias in modernization studies: Premigration differences in morphology and blood pressure among 15-30 year-old American Samoans.

Premigration differences in anthorpometry and blood pressure are examined for evidence of selective migration for biological characteristics. We conducted a 5-years follows-up of the migration status of 99 American Samoans 15-30 years old who had been previously examined in 1981 and found that 33 had migrated. Analysis of covariance of the baseline anthorpometry and blood pressures of the nonmigrants (n = 58) and those who subsequently migrated (n = 29) indicates that selective migration does occur among young American Samoan adults. Migrants of both sexes tended to be younger and leaner and had significantly lower mean blood pressures than nonmigrants even before migration. Selective migration of lean individuals with lower blood pressures may contribute to the lower blood pressures of migrants from American Samoa living in Hawaii or to the heterogeneity in other Samoan populations. These results are one of the few examples of biological selectivity demonstrated to date and illustrate the dangers of assuming that the effects of selective migration are negligible in studies of migration and health.

Stress and changing lifestyles in the Pacific: Physiological stress responses of Samoans in rural and urban settings.

The lifestyles and social environments of Pacific Islanders have changed profoundly as a result of local development and migration to urban, cosmopolitan centers. These changes have often been accompanied by an increase in chronic diseases, alcoholism, and suicide. As a result, the health effects of psychological and physiological stress have become an increasing concern in Pacific Island nations and in countries with significant Pacific migrant communities. Several studies in the Samoan Studies Project have examined catecholamine excretion rates in order to understand how the behavioral, psychological, and environmental changes of modernization affect the physiological stress responses of young Samoan adults. The results of studies in rural and urban Western Samoa, American Samoa, and Honolulu, Hawaii show that several complex factors associated with urban, more cosmopolitan lifestyles tend to increase stress hormone levels. Specifically, lifestyle differences in physical activity, diet, and social interaction have significant independent and interactive contributions. These behavioral factors can lead to a high degree of day-to-day variability in catecholamine excretion. The implications of these findings for future research designs are discussed. However, the data suggest that it is a complex interaction of lifestyle factors, not any specific single factor, that determines the physiological stress responses of Samoans in different environments. © 1993 Wiley-Liss, Inc.

Familial aggregation of bothersome benign prostatic hyperplasia symptoms.

OBJECTIVES: To evaluate familial aggregation and the mode of inheritance of bothersome benign prostatic hyperplasia (BPH). METHODS: During an extension of the North American Finasteride Trial, 301 of 895 patients and 158 spousal controls completed a family history questionnaire. Segregation analysis was performed to examine the mode of inheritance in first-degree relatives of the 301 probands. RESULTS: The lifetime cumulative probability of bothersome BPH was similar in relatives of those with BPH (0.35; 95% confidence interval [CI] 0.28 to 0.44) and spousal controls (0.36; 95% CI 0.22 to 0.56), but the age of onset was significantly earlier in relatives of cases than controls (P = 0.001). Fathers of those with BPH had a significantly elevated risk of bothersome BPH (unadjusted odds ratio [OR] 2.1; 95% CI 1.2 to 3.8) and brothers had a significantly elevated risk of both bothersome BPH (OR 3.5; 95% CI 1.7 to 7.3) and transurethral resection of the prostate (OR 3.6; 95% CI 1.4 to 8.8). After adjusting for family size, the risk of bothersome BPH increased approximately twofold with each additional affected first-degree relative (0 relatives, OR 1.0; 1 relative, OR 1.7; 2 relatives, OR 4.7). Segregation analysis suggested a rare autosomal codominant allele (frequency 0.0004). CONCLUSIONS: These findings confirm previous findings that family history and early age of onset are associated with an increased risk of BPH and that the most likely mode of inheritance is autosomal dominant or codominant. Bothersome BPH appears to have a weaker genetic component than more restrictive definitions of hereditary BPH. Thus, linkage studies are more likely to be successful if they focus on stricter definitions of hereditary BPH (eg, early onset, large volume, strong family history) rather than symptomatic or clinical BPH.